Implications for the function of histone demethylase PHF2 in malignant cancer cell

组蛋白去甲基化酶 PHF2 在恶性癌细胞中的功能意义

• 批准号: 23701038
• 负责人: OKAMOTO Kengo
• 金额: $ 2.83万
• 依托单位: Takasaki University of Health and Welfare
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23701038/
• 关键词: PHF2; JmjC; エピジェネティクス; ヒストン修飾; rRNA転写; jmjC; ヒストン; 脱メチル化

The rate-limiting step in ribosome biogenesis is the transcription of ribosomal RNA, which is controlled by environmental conditions. Regulation of cell growth ultimately depends on the control of ribosome synthesis. One key component of chromatin structures in biological regulation is the methylation of lysine residues in histone proteins, the JmjC domain-containing enzymes can catalyze histone demethylation. The jmjC enzyme PHF2 is localized in nucleoli, but its function is unclear. Here, I demonstrate that PHF2 bound to the rDNA promoter, and PHF2 contribute to pre-rRNA synthesis. Moreover, microarray analyses revealed that more than 2000 gene had altered expression in a PHF2 knockdown cells. These results suggest that PHF2 functions as a positive regulator of ribosome biogenesis, and is essential for cell proliferation.

核糖体生物发生的限速步骤是核糖体RNA的转录，这是由环境条件控制的。细胞生长的调控最终取决于对核糖体合成的控制。组蛋白中赖氨酸残基的甲基化是染色质结构生物学调控的一个关键组成部分，含JmjC结构域的酶可以催化组蛋白去甲基化。jmjC酶PHF2定位于核仁，但其功能尚不清楚。在这里，我证明了PHF2与rDNA启动子结合，并且PHF2有助于pre-rRNA的合成。此外，微阵列分析显示，超过2000个基因在PHF2敲低细胞中表达改变。这些结果表明，PHF2是核糖体生物发生的积极调节因子，对细胞增殖至关重要。